But there was some improvement in vibration perception threshold

Adults with type 1 diabetes and peripheral neuropathy who took C-peptide supplements for 1 year saw improvement in a test to measure neuropathy, but no improvement in several other markers in a randomized trial.

In the trial, 250 patients were randomized to a high or low dose of long-acting C-peptide or to placebo and had no improvement in bilateral sural nerve conduction velocity (SNCV), in the Clinical Neuropathy Score (mTCNS), or in other electrophysiological variables in the intervention group, reported John Wahren, MD, PhD, from the Karolinska Institutet Stockholm, and colleagues.

The lackluster results weren't a surprise. Cebix, which funded the study, closed its doors nearly a year ago after raising $50 million for this phase IIb trial only to announce that the drug, known as Ersatta, didn't outperform placebo. Cebix's offices in La Jolla, Calif., shut down shortly after the announcement, though Cebix AB, based in Sweden, continues to operate.

In better news, treatment was associated with a 25% improved vibration perception threshold (VPT) at the end of the 52-week study (Delta for the combined C-peptide groups was -4.5±1.0μm versus -0.1±0.9 μm, P<0.001), the authors wrote inDiabetes Care.

In an email to MedPage Today, Wahren, who was a Cebix employee at the time of the study, wrote that previous studies showed a clear distinction between C-peptide and placebo, but in the latest trial, both placebo and C-peptide seemed to improve outcomes.

Specifically, SNCV increased by 1.0±0.24 m/s (P<0.001 within group) in the two groups receiving C-peptide, but it also similarly increased in the placebo group (1.2±0.29 m/s).

"Blood glucose levels, HbA1c, and blood lipids were no different in the groups, so we have no rational explanation for the placebo effect," Wahren wrote.

"There is no disease-modifying therapy available for diabetic neuropathy and the unmet medical need is great," he added. "The present results and earlier findings suggest that future development of C-peptide as a therapeutic agent for diabetic nerve impairment should focus on small fiber neuropathy and early stages of the disorder."

Trial participants were ages 18 to 65 and had type 1 diabetes for a minimum of 4 years, with a stable diabetic regimen that provided good glucose control. At baseline, no participants were on other medications that might have influenced nerve function. The trial enrolled people from 32 sites, most of them in the U.S., and some in Canada and Sweden.

Those receiving a low dose received a subcutaneous weekly dosage of 0.8 mg, while those in this high dose group received 2.4 mg.

Plasma C-peptide rose in the low group from 1.8 to 2.2 nmol/L and from 5.6 to 6.8 nmol/L in the high dose group. There were no significant between-group differences in age, sex distribution, body mass index, blood lab results, or electrophysiological measurements at baseline.

Reports of pain and sexual function scores did not change over the duration of the study. There were treatment-related adverse events in all three groups, ranging in prevalence from 11.3% to 16.4%. The most common events were nasopharyngitis, upper respiratory tract infection, and nausea. Nonsevere hypoglycemic events occurred in 66%-74% of the participants depending on the group.

The authors noted that the improvements in VPT despite nonsignificant changes in SNCV were striking. "This finding may reflect differences in the mechanisms of conduction versus transduction of neural impulses," they wrote.

The study was supported by Cebix. Wahren and some co-authors were company employees at the time of the study.

Wahren and co-authors disclosed no relevant relationships with industry.

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